Abstract
BackgroundIt remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).MethodsWe included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987–1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.ResultsOver a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049–1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028–1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132–1.740) and 1.742 (1.294–2.344), respectively] after multivariate adjustments for traditional PAD risk factors.ConclusionsHigher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.Trial registration: Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.
Highlights
It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD)
Participants in a higher TyG index quartile had a higher prevalence of hypertension, diabetes, coronary heart disease (CHD), and stroke; and were more prone to take antihypertensive drugs, and lipid-lowering drugs
In the multivariate model that measured TyG index as a continuous variable, a 1-SD increase in TyG index was associated with an 11.9% higher risk of incident PAD after full adjustment for Quartile 1 (n = 3080) Quartile 2 (n = 3080) Quartile 3 (n = 3080) Quartile 4 (n = 3080) P value (n = 12,320)
Summary
It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD). Peripheral artery disease (PAD) is an important manifestation of systemic atherosclerosis affecting an estimated over 200 million people worldwide [1, 2] It is associated with significant cardiovascular morbidity and mortality, with a variable spectrum of symptoms from none to severe when patients present with claudication or critical limb ischemia [3]. Growing evidence has demonstrated that the TyG index is related to morbidity and mortality of cardiovascular disease in the general population, patients with and those without diabetes [12, 13] This is possibly because elevated TyG index by itself contributes to systemic arterial atherosclerosis, including carotid atherosclerosis and coronary artery calcification, an established marker of subclinical atherosclerosis [14, 15]. Long-term specific prospective studies on the relationship between PAD and the TyG index, and its trajectory derived from the multiple measurements over time have not been performed
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